Cytoprotective effect and increase of survival of neurons in the Central Nervous System (CNS) of mammals following ischemia (as in stroke), by low energy laser (LEL) irradiation.
Mammalian CNS neurons have a negligible capacity to regenerate following lesion or acute ischemic (no oxygen supply) conditions. A dramatic decrease or complete abolishment of oxygen supply to the nerve cells and other cells in a certain region of the brain can occur due to occlusion of one or more of the arteries that supply blood to the brain (Fisher M, xe2x80x9cCharacterizing the Target of Acute Stroke Therapyxe2x80x9d, Stroke, Vol. 28 No 4 pp. 866-872, April 1997). Concomitantly with this event, the neurons of the brain go through a gradual degeneration process that eventually leads to necrosis in the acute ischemic zone. Clinical syndromes such as paraplegia, quadriplegia, etc., are evident due to dysfunction of the nerve cells in the brain.
The mammalian CNS also has a negligible capacity to regenerate following injury. Limited regeneration of peripheral axons in mammals and CNS in lower vertebrate can take place in a post trauma setting.
Low energy laser irradiation has recently been found to modulate various processes in different biological systems, (Belkin, et al, A critical review of low energy laser bioeffects. Lasers Light Ophthalmology vol. 2 p. 63-71, 1988 and Conlan et al, Biostimulation of wound healing by low energy laser irradiation, Journal of Clinical Periodontology vol. 23, p. 492-496, 1996). The effect of low energy laser irradiation following trauma has been investigated so far in skin, peripheral nerves and skeletal muscles.
Assia et al (Temporal parameters of low energy laser irradiation for optimal delay of post traumatic degeneration of lto rat optic nerve, Brain Research 476: 205-212, 1989) described the possibility of delaying the post traumatic process of degeneration and scar tissue formation of a crushed optic nerve (peripheral nervous system) by low energy laser irradiation.
U.S. Pat. No. 5,580,555 to Schwartz involves the administration of tumor necrosis factor (TNF) to the sight of injury in the optic nerve in order to facilitate regeneration of axons across the sight of the injury. The use of low energy laser in conjunction with the use of the TNF is suggested to augment the effect of TNF. However, Schwartz presents no experimental results to favor the beneficial effect of the laser. Furthermore, it is described in the detailed description that treatment with TNF alone (without laser irradiation) gives good results.
It has previously been suggested that regeneration of injured peripheral nerves can-be accelerated by LEL (Rochkind S. Stimulation effect of laser energy on the regeneration of traumatically injured peripheral nerves. The Krim National Medical Inst., Morphogenesis and Regenerations Vol. 73: pp. 48-50, 1978). Nissan M., Rochkind S. et al (HeNe laser irradiation delivered transcutaneously: its effect on sciatic nerve of rats. Laser. Surg. Med. Vol. 6: pp. 435-438, 1986) also demonstrated that transcutaneous LEL of sciatic nerve induced an increase in the amplitude of the electrical signals recorded in the irradiated nerve, i.e. increased the size of the action potential.
U.S. Pat. No. 4,966,144 to Rochkind et aL. deals with a method of inducing functional regeneration of nerve fibers of an injured sight of the spinal cord (or using grafts of peripheral nerves which were placed into the injured sight) by a light source which generates light at a wavelength of 330-1200 nm. The method involves only the spinal cord but not the brain. Moreover, the method is not related to an acute ischemic phase of nerve cells in the CNS as in a situation of xe2x80x9cstrokexe2x80x9dnor is the cytoprotective effect of laser irradiation cited in Rochkind et aL
It has previously been reported that the low energy laser irradiation causes a decrease in the inflammatory response following injury to skeletal muscles (Bibikova A. and U. Oron. Promotion of muscle regeneration following cold injury to the toad (Bufo Viridis) gastrocnemius muscle by low energy laser irradiation. Anat. Rec. (1993) vol. 235 pp. 374-380 and N. Weiss and Oron Enhancement of muscle regeneration in the rat gastrocnemius muscle by low energy laser irradiation. Anat. Embryol. (1992) Vol. 186 pp. 497-503). The above phenomenon may suggest possible cytoprotective effect of at least the mitochondria and maybe other structures of the cell by the LEL. Thus, LEL irradiation allows cells under stressful conditions of low or no oxygen supply to maintain their viability in spite of the harsh conditions. The irradiated cells most probably do not degenerate to the same extent as the non-irradiated cells and therefore also the inflammatory response, which is typical to tissues undergoing a degenerative process following injury is markedly decreased. Furthermore, LEL irradiation has been found to enhance the process of formation of new blood vessels (angiogenesis) in injured skeletal muscles (Bibikova A, Belkin A. and Oron U. Enhancement of angiogenesis in regenerating gastrocnemius muscle of the toad (Bufo Viridis) by low energy laser irradiation. Anat. Embryol. (1994) Vol. 190 pp. 597-602).
So far, despite significant research efforts for many years worldwide, a safe and effective method of inhibiting or eliminating the adverse irreversible effects of stroke and other ischemic events on brain cells and the significant clinical manifestations of it on animal and human body function has yet to be developed.
The present invention seeks to provide a novel method and apparatus for using LEL irradiation to protect cells under acute ischemic conditions in the brain. In accordance with the present invention, in the initial phase of ischemia, the LEL irradiation causes an enhanced angiogenesis process which in turn causes a regeneration process in the injured brain cells in the ischemic zone, thereby allowing for greater protection of the cells in the future.
There is thus provided in accordance with a preferred embodiment of the present invention apparatus for treatment of an ischemic region of brain cells in a cranium, including a skull covering adapted to cover at least part of a cranium, at least one guide attached to the skull covering, and a laser source which is operative to direct a laser beam through the at least one guide into a cranium. The at least one guide may include an optic fiber or a waveguide.
In accordance with a preferred embodiment of the present invention the laser source includes a diode laser.
Further in accordance with a preferred embodiment of the present invention a laser controller is operatively connected to the laser source which controls operation of the laser source.
Still further in accordance with a preferred embodiment of the present invention an actuator which is operative to move the laser source further from or closer to a cranium.
Additionally in accordance with a preferred embodiment of the present invention the skull covering includes sealing material at a skull-contacting periphery thereof.
In accordance with a preferred embodiment of the present invention a timer is mounted on the skull covering.
Further in accordance with a preferred embodiment of the present invention an indicator light is mounted on the skull covering.
Still further in accordance with a preferred embodiment of the present invention a plurality of the guides are attached to the skull covering which direct a plurality of the laser beams in a plurality of directions.
Additionally in accordance with a preferred embodiment of the present invention a plurality of the guides are attached to the skull covering which are operative to focus a plurality of the laser beams in a plurality of focal lengths into a cranium.
In accordance with a preferred embodiment of the present invention a plurality of the guides are commonly attached to the laser source.
Further in accordance with a preferred embodiment of the present invention a plurality of the laser sources and a plurality of the guides are provided, wherein each source directs a laser beam through one the guide.